Heart aging is characterized by structural and diastolic dysfunction of the heart. However, there is still no effective drug to prevent and treat the abnormal changes in cardiac function caused by ...aging. Here, we present the preventive effects of emodin and its derivative Kanglexin (KLX) against heart aging. We found that the diastolic dysfunction and cardiac remodeling in mice with D-galactose (D-gal)-induced aging were markedly mitigated by KLX and emodin. In addition, the senescence of neonatal mouse cardiomyocytes induced by D-gal was also reversed by KLX and emodin treatment. However, KLX exhibited better anti-heart aging effects than emodin at the same dose. Dysregulated mitophagy was observed in aging hearts and in senescent neonatal mouse cardiomyocytes, and KLX produced a greater increase in mitophagy than emodin. The mitophagy-promoting effects of KLX and emodin were ascribed to their abilities to enhance the protein stability of Parkin, a key modulator in mitophagy, with different potencies. Molecular docking and SPR analysis demonstrated that KLX has a higher affinity for the ubiquitin-like (UBL) domain of Parkin than emodin. The UBL domain might contribute to the stabilizing effects of KLX on Parkin. In conclusion, this study identifies KLX and emodin as effective anti-heart aging drugs that activate Parkin-mediated mitophagy and outlines their putative therapeutic importance.
Current knowledge on responses of aquatic clonal plants to resource availability is largely based on studies manipulating limited resource levels, which may have failed to capture the "big picture" ...for aquatic clonal plants in response to resource availability. In a greenhouse experiment, we grew the floating clonal plant Spirodela polyrhiza under ten nutrient levels (i.e., 1/64x, 1/32x, 1/16x, 1/8x, 1/4x, 1/2x, 1x, 2x, 4x and 8xfull-strength Hoagland solution) and examined their responses in terms of clonal growth, morphology and biomass allocations. The responses of total biomass and number of ramets to nutrient availability were unimodal. A similar pattern was found for frond mass, frond length and frond width, even though area per frond and specific frond area fluctuated greatly in response to nutrient availability. In contrast, the responses of root mass and root length to nutrient availability were U-shaped. Moreover, S. polyrhiza invested more to roots under lower nutrient concentrations. These results suggest that nutrient availability may have distinct influences on roots and fronds of the aquatic clonal plant S. polyrhiza, resulting in a great influence on the whole S. polyrhiza population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aqueous solution syntheses are mostly based on mixing two solutions with different reactants. It is shown that freezing one solution and melting it in another solution provides a new interesting ...strategy to mix chemicals and to significantly change the reaction kinetics and thermodynamics. For example, a precursor solution containing a certain concentration of AgNO3 was frozen and dropped into a reductive NaBH4 solution at about 0 °C. The ultra‐slow release of reactants was successfully achieved. An ice‐melting process can be used to synthesize atomically dispersed metals, including cobalt, nickel, copper, rhodium, ruthenium, palladium, silver, osmium, iridium, platinum, and gold, which can be easily extended to other solution syntheses (such as precipitation, hydrolysis, and displacement reactions) and provide a generalized method to redesign the interphase reaction kinetics and ion diffusion in wet chemistry.
Freezing one solution and melting it in another provides a strategy to mix chemicals and to significantly change the reaction kinetics and thermodynamics. For example, a AgNO3 solution was frozen and dropped into a reductive NaBH4 solution at about 0 °C. Atomically disperse metals can be synthesized in this fashion, and the method can be extended to other solution syntheses (precipitation, hydrolysis, and displacement reactions).
We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 ...controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that ...regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo.
Veterinary antibiotics are intensively and widely used in animal farming to treat or prevent diseases, as well as improve growth rate and feed efficiency. Animal manure is an important reservoir of ...veterinary antibiotics due to their high excretion rates, and thus manure application has been a critical source of veterinary antibiotics in agro-ecosystems. However, how veterinary antibiotics affect agroecosystem functions is still unclearly understood. In this study, we evaluated the effects of veterinary antibiotics on soil bacteria and earthworms in agricultural land with long-term manure application. The potential mechanisms of antibiotic-induced changes in crop yields were also revealed. The results showed that the increasing prevalence of veterinary antibiotics in agro-ecosystems inhibited earthworm abundance and bacterial diversity, and then decreased the bioavailability of soil nutrients. Furthermore, high-dose exposure to veterinary antibiotics improved the abundance of plant pathogenic bacteria. Analysis indicated that veterinary antibiotics played an important underlying role in driving the negative effects on peanut grain yields via disturbing microbe- and earthworm-mediated soil available nutrient contents. The direct toxicity effects of antibiotics on peanut relative yields were stronger than their indirect mediating effects. Additionally, the tradeoffs between antibiotics and agroecosystem functions increased at low exposure levels and then decreased at high exposure levels, which indicated the effects of antibiotics on agroecosystem functions were dose-dependent, except for earthworm biomass. Antibiotic contamination which will impose threats to agricultural sustainability was highlighted and should be paid more attention.
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•Veterinary antibiotics change earthworm abundance and bacterial diversity in agroecosystem.•Antibiotics affect crop yields by modifying earthworm/microbe-mediated available nutrients.•Antibiotics enhance ecosystem functions at low levels but inhibit at high levels.
Cereal straw is one of the most abundant biomass burned in China but its contribution to fine particulates is not adequately understood. In this study, three main kinds of cereal straws were ...collected from five grain producing areas in China. Fine particulate matters （PMzs） from the cereal straws subjected to control burnings, both under smoldering and flaming status, were sampled by using a custom made dilution chamber and sampling system in the laboratory. Element carbon （EC） and organic carbon （OC） was analyzed. 141 compounds of organic matters were measured by gas chromatography-mass spectrum （GC-MS）. Source profiles of particulate organic matters emitted from cereal straw burnings were obtained. The results indicated that organic matters contribute a large fraction in fine particulate matters. Levoglucosan had the highest contributions with averagely 4.5% in mass of fine particulates and can be considered as the tracer of biomass burnings. Methyloxylated phenols from lignin degradation also had high concentrations in PM2.5, and contained approximately equal amounts of guaiacyl and syringyl compounds. 13-Sitostrol also made up relatively a large fraction of PMz5 compared with the other sterols （0.18%-0.63% of the total fine particle mass）. Normal alkanes, PAHs, fatty acids, as well as normal alkanols had relatively lower concentrations compared with the compounds mentioned above. Carbon preference index （CPI） of normal alkanes and alkanoic acids showed characteristics of biogenic fuel burnings. Burning status significantly influenced the formations of EC and PAHs. The differences between the emission profiles of straw and wood combustions were displayed by the fingerprint compounds, which may be used to identify the contributions between wood and straw burnings in source apportionment researches.
Gefitinib (Iressa, ZD-1839), a small molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) pathway, is currently under investigation in clinical trials for the ...treatment of colorectal cancer (CRC). However, as known, some patients develop resistance to TKIs, and the mechanisms mediating intrinsic resistance to EGFR-TKIs in CRC have not been fully characterized. Resistance to EGFR inhibitors reportedly involves activation of signal transducer and activator of transcription 3 (STAT3) in glioma and lung cancer. Here, we demonstrated that the nuclear pyruvate kinase isoform M2 (PKM2) levels were positively correlated with gefitinib resistance in CRC cells. The overexpression of nuclear PKM2 in HT29 cells decreased the effect of gefitinib therapy, whereas PKM2 knockdown increased gefitinib efficacy. Furthermore, the activation of STAT3 by nuclear PKM2 was associated with gefitinib resistance. Inhibition of STAT3 by Stattic, a STAT3-specific inhibitor, or STAT3-specific siRNA sensitized resistant cells to gefitinib. These results suggest that nuclear PKM2 modulates the sensitivity of CRC cells to gefitinib and indicate that small molecule pharmacological disruption of nuclear PKM2 association with STAT3 is a potential avenue for overcoming EGFR-TKI resistance in CRC patients.
Li Dong Wang and colleagues report a genome wide association study for esophageal squamous cell carcinoma in the Chinese population. They identify two risk loci at PLCE1 and C20orf54.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Veterinary antibiotics have been detected as contaminants of emerging concern in soil environment worldwide. Animal manure is frequently applied to agricultural fields to improve soil fertility, ...which can result in introducing large amount of antibiotics into soil environment. However, few attempts have been made to identify the spatial and temporal dynamics of veterinary antibiotics in soil at the hillslope scale with different land uses. This study was performed to explore the pattern and variability of veterinary antibiotics in the soil in response to rainfall events. Results showed that higher concentrations of veterinary antibiotics were generally found in cropland (292.6 ± 280.1 ng/g) and orchard (228.1 ± 230.5 ng/g) than in forestland (13.5 ± 9.9 ng/g). After rainfall events, antibiotics accumulated in the soil at the positions where manure was applied, especially under high-intensity rainfall conditions. However, the antibiotic concentration in soil slightly increased from the top to the bottom of hills, thus indicating the restricted contribution of runoff to antibiotic transport, especially under low-intensity rainfall conditions. In addition, most antibiotics were sequestered in the surface soil (0–10 cm), and higher antibiotic concentrations were observed in deep soil (20–40 cm) in cropland than orchard. The soil aggregate, organic matter, and clay content played important roles in antibiotic sequestration along the hillslope subject to low-, medium-, and large-amount rainfall events, respectively. This study identified that land use, rainfall conditions, and soil structures jointly affect the spatial and temporal variability of antibiotics in soils on hillslopes.
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•Spatial variability of antibiotics in soil was demonstrated at the hillslope scale.•Antibiotics accumulated in the soil at the manure-amended hillslope positions.•Rainfall characteristics affected persistence of antibiotics in hillslope soil.•Soil structure modified by rainfall events correlated with variability of antibiotics.
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